Khalid Shah, MS, PhD

Malignant glioblastomas have virtually defied all therapeutic modalities to date. Successful therapies will need novel strategies targeting the underlying pathogenesis which may ultimately offer an innovative approach for glioblastoma patients.  

This proposal aims at using neural stem cells to deliver therapeutic drugs that can stop tumor cells to proliferate and simultaneously kill them while leaving the normal brain cells intact. This will be combined with novel in vivo imaging methods that will allow us to monitor the location and size of tumors and track the migration of neural stem cell delivery vehicles in experimental animal models.  

There are four basic components of the proposed therapeutic system.  

• First, the “shell” of a virus, will be used to efficiently carry therapeutic and imaging genes into cells.  
• Second, neural stem cells will be employed as delivery vehicles as they have been found to home to tumor cells in the brain and can change themselves into normal cells of the nervous system.  
• Third, engineered apoptotic and anti-proliferative proteins that are released at the tumor destination by the delivery cells will be employed which will stop tumor cells to divide and selectively kill them while leaving the normal brain cells intact.  
• Fourth, fluorescent and bioluminescent markers will be incorporated into tumor cells and delivery cells such that we can monitor their fate in the brains in real time.  

Although these studies are experimental, we can envision a therapeutic modality in which the main tumor mass in the brains of patients will be removed at the time of surgery and therapeutic neural stem cells will be introduced near the remaining tumor cells thus eliminating the risk of recurrence. This will have a major impact in developing more efficient means of eradicating gliomas and saving the lives of many brain cancer patients.  

This Alliance for Cancer Gene Therapy Research Fellow is funded in part by Swim Across America.